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3 results on '"Wijkander M"'

1. Ancient and recent differences in the intrinsic susceptibility of Mycobacterium tuberculosis complex to pretomanid.

Author

Bateson A, Ortiz Canseco J, McHugh TD, Witney AA, Feuerriegel S, Merker M, Kohl TA, Utpatel C, Niemann S, Andres S, Kranzer K, Maurer FP, Ghodousi A, Borroni E, Cirillo DM, Wijkander M, Toro JC, Groenheit R, Werngren J, Machado D, Viveiros M, Warren RM, Sirgel F, Dippenaar A, Köser CU, Sun E, and Timm J

Subjects
Antitubercular Agents pharmacology, Humans, Microbial Sensitivity Tests, Mycobacterium tuberculosis genetics, Nitroimidazoles, Tuberculosis microbiology
Abstract

Objectives: To develop a robust phenotypic antimicrobial susceptibility testing (AST) method with a correctly set breakpoint for pretomanid (Pa), the most recently approved anti-tuberculosis drug., Methods: The Becton Dickinson Mycobacterial Growth Indicator Tube™ (MGIT) system was used at six laboratories to determine the MICs of a phylogenetically diverse collection of 356 Mycobacterium tuberculosis complex (MTBC) strains to establish the epidemiological cut-off value for pretomanid. MICs were correlated with WGS data to study the genetic basis of differences in the susceptibility to pretomanid., Results: We observed ancient differences in the susceptibility to pretomanid among various members of MTBC. Most notably, lineage 1 of M. tuberculosis, which is estimated to account for 28% of tuberculosis cases globally, was less susceptible than lineages 2, 3, 4 and 7 of M. tuberculosis, resulting in a 99th percentile of 2 mg/L for lineage 1 compared with 0.5 mg/L for the remaining M. tuberculosis lineages. Moreover, we observed that higher MICs (≥8 mg/L), which probably confer resistance, had recently evolved independently in six different M. tuberculosis strains. Unlike the aforementioned ancient differences in susceptibility, these recent differences were likely caused by mutations in the known pretomanid resistance genes., Conclusions: In light of these findings, the provisional critical concentration of 1 mg/L for MGIT set by EMA must be re-evaluated. More broadly, these findings underline the importance of considering the global diversity of MTBC during clinical development of drugs and when defining breakpoints for AST., (© The Author(s) 2022. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

Published
2022
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2. A crowd of BashTheBug volunteers reproducibly and accurately measure the minimum inhibitory concentrations of 13 antitubercular drugs from photographs of 96-well broth microdilution plates

Author

Fowler, P.W., Wright, C., Spiers, H., Zhu, T., Baeten, E.M.L., Hoosdally, S.W., Cruz, A.L.G., Roohi, A., Kouchaki, S., Walker, T.M., Peto, T.E.A., Miller, G., Lintott, C., Clifton, D., Crook, D.W., Walker, A.S., Barilar, I., Battaglia, S., Borroni, E., Brandao, A.P., Brankin, A., Cabibbe, A.M., Carter, J., Chetty, D., Cirillo, D.M., Claxton, P., Clifton, D.A., Cohen, T., Coronel, Jorge, Dreyer, V., Earle, S.G., Escuyer, V., Ferrazoli, L., Gao, G.F., Gardy, J., Gharbia, S., Ghisi, K.T., Ghodousi, A., Grandjean, Louis, Grazian, C., Groenheit, R., Guthrie, J.L., He, W., Hoffmann, H., Hoosdally, S.J., Martinhunt, M., Iqbal, Z., Ismail, N.A., Jarrett, L., Joseph, L., Jou, R., Kambli, P., Khot, R., Knaggs, J., Koch, A., Kohlerschmidt, D., Lachapelle, A.S., Lalvani, A., Lapierre, S.G., Laurenson, I.F., Letcher, B., Lin, W.-H., Liu, C., Liu, D., Malone, K.M., Mandal, A., Mansjõ, M., Matias, D., Meintjes, G., Mendes, F.D.F., Merker, M., Mihalic, M., Millard, J., Miotto, P., Mistry, N., Moore, David Alexander James, Musser, K.A., Ngcamu, D., Nhung, H.N., Niemann, S., Nilgiriwala, K.S., Nimmo, C., O’Donnell, M., Okozi, N., Oliveira, R.S., Omar, S.V., Paton, N., Pinhata, J.M.W., Plesnik, S., Puyen, Z.M., Rabodoarivelo, M.S., Rakotosamimanana, N., Rancoita, P.M.V., Rathod, P., Robinson, E., Rodger, G., Rodrigues, C., Rodwell, T.C., Santos-Lazaro, D., Shah, S., Kohl, T.A., Smith, G., Solano, Walter, Spitaleri, A., Supply, P., Steyn, A.J.C., Surve, U., Tahseen, S., Thuong, N.T.T., Thwaites, G., Todt, K., Trovato, A., Utpatel, C., Van Rie, A., Vijay, S., Warren, R., Werngren, J., Wijkander, M., Wilkinson, R.J., Wilson, D.J., Wintringer, P., Xiao, Y.-X., Yang, Y., Yanlin, Z., Yao, S.-Y., Zhu, B., The Zooniverse Volunteer Community, The CRyPTIC Consortium, Community, The Zooniverse Volunteer, Consortium, The CRyPTIC, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), and Wellcome Trust

Subjects
Volunteers, Model organisms, infectious disease, [SDV]Life Sciences [q-bio], Immunology, Antitubercular Agents, Infectious Disease, Microbial Sensitivity Tests, Zooniverse Volunteer Community, 0601 Biochemistry and Cell Biology, antibiotics, General Biochemistry, Genetics and Molecular Biology, Imaging, minimum inhibitory concentrations, antitubercular drugs, citizen science, M. tuberculosis, Humans, clinical microbiology, Human Biology & Physiology, General Immunology and Microbiology, CRyPTIC Consortium, Prevention, General Neuroscience, FOS: Clinical medicine, microbiology, BashTheBug, Mycobacterium tuberculosis, General Medicine, microdilution plates, Emerging Infectious Diseases, Infectious Diseases, Good Health and Well Being, tuberculosis, 5.1 Pharmaceuticals, photographs, Antimicrobial Resistance, Biochemistry and Cell Biology, Development of treatments and therapeutic interventions, Infection
Abstract

Tuberculosis is a respiratory disease that is treatable with antibiotics. An increasing prevalence of resistance means that to ensure a good treatment outcome it is desirable to test the susceptibility of each infection to different antibiotics. Conventionally, this is done by culturing a clinical sample and then exposing aliquots to a panel of antibiotics, each being present at a pre-determined concentration, thereby determining if the sample isresistant or susceptible to each sample. The minimum inhibitory concentration (MIC) of a drug is the lowestconcentration that inhibits growth and is a more useful quantity but requires each sample to be tested at a range ofconcentrations for each drug. Using 96-well broth micro dilution plates with each well containing a lyophilised pre-determined amount of an antibiotic is a convenient and cost-effective way to measure the MICs of several drugs at once for a clinical sample. Although accurate, this is still an expensive and slow process that requires highly-skilled and experienced laboratory scientists. Here we show that, through the BashTheBug project hosted on the Zooniverse citizen science platform, a crowd of volunteers can reproducibly and accurately determine the MICs for 13 drugs and that simply taking the median or mode of 11-17 independent classifications is sufficient. There is therefore a potential role for crowds to support (but not supplant) the role of experts in antibiotic susceptibility testing.Tuberculosis is a bacterial respiratory infection that kills about 1.4 million people worldwide each year. While antibiotics can cure the condition, the bacterium responsible for this disease

Published
2022
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3. Epidemiological cut-off values for a 96-well broth microdilution plate for high-throughput research antibiotic susceptibility testing of

Author

Fowler, P.W., Barilar, I., Battaglia, S., Borroni, E., Brandao, A.P., Brankin, A., Cabibbe, A.M., Carter, J., Cirillo, D.M., Claxton, P., Clifton, D.A., Cohen, T., Coronel, Jorge, Crook, D.W., Dreyer, V., Earle, S.G., Escuyer, V., Ferrazoli, L., Gao, G.F., Gardy, J., Gharbia, S., Ghisi, K.T., Ghodousi, A., Cruz, A.L.G., Grandjean, Louis, Grazian, C., Groenheit, R., Guthrie, J.L., He, W., Hoffmann, H., Hoosdally, S.J., Hunt, M., Iqbal, Z., Ismail, N.A., Jarrett, L., Joseph, L., Jou, R., Kambli, P., Khot, R., Knaggs, J., Koch, A., Kohlerschmidt, D., Kouchaki, S., Lachapelle, A.S., Lalvani, A., Lapierre, S.G., Laurenson, I.F., Letcher, B., Lin, W.-H., Liu, C., Liu, D., Malone, K.M., Mandal, A., Mansjö, M., Matias, D., Meintjes, G., de Freitas Mendes, F., Merker, M., Mihalic, M., Millard, J., Miotto, P., Mistry, N., Moore, David Alexander James, Musser, K.A., Ngcamu, D., Nhung, H.N., Niemann, S., Nilgiriwala, K.S., Nimmo, C., Okozi, N., Oliveira, R.S., Omar, S.V., Paton, N., Peto, T.E.A., Pinhata, J.M.W., Plesnik, S., Puyen, Z.M., Rabodoarivelo, M.S., Rakotosamimanana, N., Rancoita, P.M.V., Rathod, P., Robinson, E., Rodger, G., Rodrigues, C., Rodwell, T.C., Roohi, A., Santos-Lazaro, D., Shah, S., Kohl, T.A., Smith, G., Solano, Walter, Spitaleri, A., Supply, P., Surve, U., Tahseen, S., Thuong, N.T.T., Thwaites, G., Todt, K., Trovato, A., Utpatel, C., Van Rie, A., Vijay, S., Walker, T.M., Walker, A.S., Warren, R., Werngren, J., Wijkander, M., Wilkinson, R.J., Wilson, D.J., Wintringer, P., Xiao, Y.-X., Yang, Y., Yanlin, Z., Yao, S.-Y., Zhu, B., Consoritum, CRyPTIC, Walker, AS, and CRyPTIC Consortium

Subjects
microdilution, Pulmonary and Respiratory Medicine, tuberculosis, Respiratory, M. tuberculosis, Humans, Tuberculosis, Human medicine, infections, Microbial Sensitivity Tests, Mycobacterium tuberculosis, Anti-Bacterial Agents
Abstract

Drug susceptibility testing ofM. tuberculosisis rooted in a binary susceptible/resistant paradigm. While there are considerable advantages in measuring the minimum inhibitory concentrations (MICs) of a panel of drugs for an isolate, it is necessary to measure the epidemiological cut-off values (ECOFF/ECVs) to permit comparison with qualitative data. Here we present ECOFF/ECVs for 13 anti-tuberculosis compounds, including bedaquiline and delamanid, derived from 20 637 clinical isolates collected by 14 laboratories based in 11 countries on five continents. Each isolate was incubated for 14 days on a dry 96-well broth microdilution plate and then read. Resistance to most of the drugs due to prior exposure is expected and the MIC distributions for many of the compounds are complex, and therefore aphenotypicallywild-type population could not be defined. Since a majority of samples also underwent genetic sequencing, we defined agenotypicallywild-type population and measured the MIC of the 99th percentile by direct measurement andviafitting a Gaussian using interval regression. The proposed ECOFF/ECVs were then validated by comparing with the MIC distributions of high-confidence genetic variants that confer resistance and with qualitative drug susceptibility tests obtainedviathe Mycobacterial Growth Indicator Tube (MGIT) system or Microscopic-Observation Drug Susceptibility (MODS) assay. These ECOFF/ECVs will inform and encourage the more widespread adoption of broth microdilution: this is a cheap culture-based method that tests the susceptibility of 12–14 antibiotics on a single 96-well plate and so could help personalise the treatment of tuberculosis.

Published
2021

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